MicroRNAs for the diagnosis, prognosis and treatment of AMLs We have discovered alterations of microRNA genes in human leukemias, have discovered that a large fraction of microRNA genes are in chromosomal regions involved in genomic alterations in cancers, have discovered somatic and germ line mutations of microRNA genes in leukemias, and have developed a microRNA platform to investigate the global expression of microRNA genes in normal and leukemic tissues. In addition, we have discovered that miR15/miR16 cause apoptosis by targeting BCL2 and that miR221 and 222 targetKIT. In this proposal we apply our platform to investigate the role of microRNA genes in the pathogenesis and progression of AMLs and to develop better prognostic indicators of these diseases. In addition, the identification of altered microRNA genes involved in the pathogenesis of AMLs could provide new, important targets for the development of novel therapies based on microRNAs or their antisense, depending on whether the pathogenetic microRNAs function as suppressors or oncogenes respectively. We have already made significant progress and have identified microRNAs that may play an important role in AML. This project is highly integrated with the other projects of this program and provides them with microRNA targets involved in the apoptotic process.